Components of biocompatibility

The second component of biocompatibility is that of material degradation. It is emphasized here that degradation is a component of biocompatibility rather than a separate phenomena. There is still confusion over this since it is often perceived that degradation, which occurs on the material side of the interface, is the counterpart to biocompatibility which is equated with the other (tissue) side. This is not correct since degradation is the counterpart to the local host response, both being contributory to the biocompatibility of the system. 

The purpose of explaining the role of the biological, or physiological environment in degradation phenomena, was to emphasize die crucial significance of the interaction between degradation and the host response, for not only can degradation be influenced by the host response but also it can control that response. 

To explain this in a little more detail, let us consider the evolution of the local host response, which is the third component of biocompatibility, using a model that involves inflammatory and repair processes (7). Whenever a material is implanted into the tissues of the body, there has to be a degree of trauma associated with the insertion process. This will inevitably establish an acute inflammatory response, which is the body s natural defence mechanism to any injury. The inflammation is totally desirable and helpful since it is the precursor to the second phase of the response, which is that of tissue repair. The response to a surgical incision is acute inflammation followed by repair, the consequences of which are a zone of fibrous (collagenous) scar tissue. If a biomaterial is placed within the tissue, this response will be modified by its presence, but the extent to which that modification occurs depends on many factors. 

Considering first the role of the material, if that material were totally inert chemically and unable to react at all with the tissues, and if the device were not able to irritate the tissues in any way, the perturbation to the inflammation/repair sequence is minimal, and the result will be the formation of a zone of fibrous tissue analogous to the scar, but oriented in such a way as to envelope the implant. The classical response to an implant is its encapsulation by soft fibrous tissue. On the other hand, if the material is able to react with the tissues, chemically, mechanically or any other way, it will act as a persistent stimulus to inflammation. While there is nothing inherently harmful about inflammation as a response to injury, persistent inflammation occurring as a response to a persistent injury is less acceptable. At the very least, this results in a continued stimulus to fibrosis such that the capsule is far more extensive and may intervene between the material and tissue it is meant to be in contact with (for example bone in the case of joint prostheses) but perhaps more importantly it can change the immediate tissue environment from one of quiescent fibrosis to that of active chronic inflammation. This is rarely the appropriate response and, as noted above, is likely to generate an even more aggressive environment. 

In the context of the definition of biocompatibility, therefore, it is important that the interaction between the material and the tissues is one which leads to an acceptable balance between inflammation and repair. A few points may serve to explain this further and qualify appropriateness. First, the nature of the host response and those features which constitute acceptability will vary very considerably from one host to another and from one location (or set of circumstances) to another within a pmticular host. It is often forgotten that host variables are as important as material variables in the determination of biocompatibility. This is particularly important when the wide variety of tissue characteristics is considered. Obviously bone is very different from nerve tissue or a vascular endothelium and there will be very considerable difference in the details of their 

The above definition of biocompatibility helps to explain the subject area but cannot describe exactly what it is. For this purpose we have to consider the various components that are involved in biocompatibility processes. Biocompatibility refers to the totality of the interfacial reactions between biomaterials and tissues and to their consequences. These reactions and consequences can be divided into four categories. These involve different mechanisms and indeed quite separate sectors of science but are, nevertheless, inter-related. 

The first component is that of the protein adsorption mentioned above. This process is initiated as soon as a material comes into contact with tissue fluids such that relatively quickly the surface of the biomaterial is covered with a layer of protein. The kinetics and extent of this process will vary from material to material which will in any case be a dynamic phenomenon with adsorption and desorption processes continuously taking place. Under some circumstances, this layer is extremely important in controlling the development of the host response since cell behavior near the material may depend on interactions with these proteins. For example, thrombogenicity is controlled by a number of events including the interaction between plasma proteins and surfaces, these proteins being able to influence the attachment of platelets to the surface. In other circumstances, the effects of this protein layer are far from clear. 

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Polyelectrolytes have been widely investigated as components of biocompatible materials. Biomaterials come into contact with blood when used as components in invasive instruments, implant devices, extracorporeal devices in contact with blood flow, implanted parts of hard structural elements, implanted parts of organs, implanted soft tissue substitutes and drug delivery devices. Approaches to the development of blood compatible materials include surface modification to give blood compatibility, polyelectrolyte-based systems which adsorb and/or release heparin as well as polyelectrolytes which mimic the biological activity of heparin. 

An edited collection of contributions dealing with the major components of biocompatibility mechanisms, including corrosion and degradation phenomena, toxicology and the local tissue response. 

The second aspect of biocompatibility is a leaching problem. Ion-selective electrode materials, especially components of solvent polymeric membranes, are subject to leaching upon prolonged contact with physiological media. Membrane components such as plasticizers, ion exchangers and ionophores may activate the clotting cascade or stimulate an immune response. Moreover, they can be potentially toxic when released to the blood stream in significant concentrations. 

Determination of the exact mechanism leading to cellular internalisation of CNTs is considered very important in their development as components of biomedical devices and therapeutics intended for implantation or administration to patients. One of the most important parameters in all such studies is the type of nanotubes used, determined by the process by which they are made biocompatible. Interactions with cells have to be performed using biocompatible CNTs, achieved by either covalent or noncovalent surface functionalisation that results in water-dispersible CNTs. A variety of different functionalisation strategies for CNTs have been reported by different groups, therefore direct comparisons are often hampered by the inability to correlate experimental conditions. 

Samples, even at moderate concentrations, injected into the HPLC column may precipitate in the mobile phase or at the column frit. In addition, the presence of other compounds (e.g., lipids) in the injection sample may drive the carotenoids out of solution or precipitate themselves in the mobile phase, trapping carotenoids. It is best to dissolve the sample in the mobile phase or a slightly weaker solvent to avoid these problems. Centrifugation or filtration of the samples prior to injection will prevent the introduction of particles that may block the frit, fouling the column and resulting in elevated column pressure. In addition to precipitation, other sources of on-column losses of carotenoids include nonspecific adsorption and oxidation. These can be minimized by incorporating modifiers into the mobile phase (Epler et al., 1993). Triethylamine or diisopropyl ethylamine at 0.1% (v/v) and ammonium acetate at 5 to 50 mM has been successful for this purpose. Since ammonium acetate is poorly soluble in acetonitrile, it should be dissolved in the alcoholic component of the mobile phase prior to mixing with other components. The ammonium acetate concentration in mobile phases composed primarily of acetonitrile must be mixed at lower concentration to avoid precipitation. In some cases, stainless steel frits have been reported to cause oxidative losses of carotenoids (Epler et al., 1992). When available, columns should be obtained with biocompatible frits such as titanium, Hastolloy C, or PEEK. 

The clinical utility of electrochemical sensors for continuous glucose monitoring in subcutaneous tissue has been limited by numerous challenges related to sensor component and biocompatibility-based failures.1,2 Sensor component failures include electrical failure, loss of enzyme activity, and membrane degradation,3 4 while examples of biocompatibility-based failures include infection, membrane biofouling (e.g., adsorption of small molecules and proteins to the sensor surface), and bbrous... 

Fluorourethanes are used in products ranging from hard, heat-resistant electrical components to biocompatible surgical adhesives. The properties of a specific flu-orourethane resin are determined by the raw materials and the manufacturing process used. 

A second index of biocompatibility was the quantitative analysis of cell growth inhibition, again on mouse fibroblast L929 cells, induced by the liquid components of the adhesive system and water extracts of two solid crosslinked materials. Table IV is a summary of the percent inhibition of cell growth (percent ICG). The mean protein values at 4 °C have been subtracted from the mean protein values (five test samples) at 37 °C for each treatment condition. The percent inhibition of cell growth (percent ICG) is shown for each treatment condition. The precision of the assay is approximately 10%. 

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